Nature Reviews Genetics 11, 773-785 (November 2010) | doi:10.1038/nrg2867

Article series: Study designs

Statistical analysis strategies for association studies involving rare variants

See also: Correspondence by Tavtigian et al.

Vikas Bansal1,4, Ondrej Libiger1,2,3,4, Ali Torkamani1,2,4 & Nicholas J. Schork1,2  About the authors


The limitations of genome-wide association (GWA) studies that focus on the phenotypic influence of common genetic variants have motivated human geneticists to consider the contribution of rare variants to phenotypic expression. The increasing availability of high-throughput sequencing technologies has enabled studies of rare variants but these methods will not be sufficient for their success as appropriate analytical methods are also needed. We consider data analysis approaches to testing associations between a phenotype and collections of rare variants in a defined genomic region or set of regions. Ultimately, although a wide variety of analytical approaches exist, more work is needed to refine them and determine their properties and power in different contexts.

Author affiliations

  1. The Scripps Translational Science Institute, 3344 North Torrey Pines Court, Suite 300, La Jolla, California 92037, USA.
  2. Department of Molecular and Experimental Medicine, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA.
  3. Lekarska Fakulta v Hradci Kralove, Charles University, Faculty of Medicine in Hradec Kralove, PO BOX 38, Simkova 870, Hradec Kralove 1, 500 38, Czech Republic.
  4. These authors contributed equally to this Review.

Correspondence to: Nicholas J. Schork1,2 Email:

Published online 13 October 2010